The role of single shot spinal anesthesia has been established in ex-premature infants at risk of apnea. However, use of epidural anesthesia in neonates is on the rise. In this systematic analysis, we have reviewed the current evidence on the safety and efficacy of the use of single shot and continuous epidural anesthesia/analgesia in neonates. Current clinical practice is guided by evidence based mostly on non-randomized studies, prospective/retrospective case series and surveys. Single shot caudal blockade as a sole technique has been used in neonates mainly for inguinal hernia repair and circumcision. Use of continuous epidural anesthesia through the caudal route or caudo-thoracic advancement of the catheter for major thoracic and abdominal surgery offers good perioperative analgesia. Other observed benefits are early extubation, attenuation of stress response, early return of bowel function and reduction of general anesthesia-related postoperative complications. However, risk of procedure-related and drug-related complications to the developing neural structure remains a serious concern.